Herpes zoster ophthalmicus uveitis: onset and complications: Herpes Zoster Uveitis.

PURPOSE: To describe the timing of uveitis onset and frequency of associated complications in individuals with herpes zoster ophthalmicus (HZO). DESIGN: Retrospective, cohort study METHODS: Individuals with acute HZO seen at the Auckland District Health Board from 2006 to 2016 were studied. The primary outcome measures were the proportion who developed uveitis and time to diagnosis of uveitis following the onset of HZO. Secondary outcome measures included complications of HZO uveitis and effects of prompt antiviral (within 72 hours) on outcomes. RESULTS: 869 patients with HZO were included for analysis, of whom 413 (47.6%) developed uveitis. Median time from onset of rash to diagnosis of uveitis was 10 days (IQR 6 - 14). Of the 658 individuals examined within the first week following rash onset (days 0 through 7), 17.6% (116/658) were diagnosed with uveitis at that initial presenting examination, with an additional 24.9% (164/658) diagnosed with uveitis at a subsequent visit. Complications were higher in eyes with uveitis, including: moderate or severe vision loss, corneal scarring, neurotrophic keratitis, band keratopathy, corneal melt, elevated intraocular pressure, glaucoma, and cataract (all p<0.01). Prompt antiviral was associated with a lower rate of moderate vision loss among eyes with uveitis (p=0.02). CONCLUSIONS: Uveitis occurred in approximately half of individuals with HZO and was most frequently diagnosed during the second week following rash onset. Eyes with uveitis were more likely to have other ocular complications and loss of vision.

A comparative evaluation of deep learning approaches for ophthalmology.

There is a growing number of publicly available ophthalmic imaging datasets and open-source code for Machine Learning algorithms. This allows ophthalmic researchers and practitioners to independently perform various deep-learning tasks. With the advancement in artificial intelligence (AI) and in the field of imaging, the choice of the most appropriate AI architecture for different tasks will vary greatly. The best-performing AI-dataset combination will depend on the specific problem that needs to be solved and the type of data available. The article discusses different machine learning models and deep learning architectures currently used for various ophthalmic imaging modalities and for different machine learning tasks. It also proposes the most appropriate models based on accuracy and other important factors such as training time, the ability to deploy the model on clinical devices/smartphones, heatmaps that enhance the self-explanatory nature of classification decisions, and the ability to train/adapt on small image datasets to determine if further data collection is worthwhile. The article extensively reviews the existing state-of-the-art AI methods focused on useful machine-learning applications for ophthalmology. It estimates their performance and viability through training and evaluating architectures with different public and private image datasets of different modalities, such as full-color retinal images, OCT images, and 3D OCT scans. The article is expected to benefit the readers by enriching their knowledge of artificial intelligence applied to ophthalmology.

Optic Atrophy From Retrograde Transsynaptic Axonal Degeneration Following Pediatric Brain Injury.

BACKGROUND: The patterns of optic atrophy due to retrograde transsynaptic degeneration (RTSD) have not been well characterized in children. This study aimed to characterize optic atrophy in pediatric patients with focal intracerebral lesions. METHODS: A retrospective review of children with optic atrophy and focal intracerebral lesions was conducted. Ophthalmic data were recorded, including visual acuity, color vision, formal automated visual fields and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell layer. RESULTS: Six patients (83.33% male) were included. The mean visual acuity (VA) of all eyes was 0.30 logMAR (20/40 Snellen), with no significant difference in the mean logMAR VA in the ipsilateral eye to the location of the lesion compared with the contralateral eye (0.30 vs 0.30, P = 1.000). Color vision (available in 5 patients) was normal in 2, mildly reduced in one and markedly reduced in 2. Bitemporal optic disc pallor was observed in 5 out of 6 patients. OCT data revealed that pRNFL thickness was most significantly diminished in the temporal (95% CI: -44.71 to -14.18 µm, P = 0.0021), inferotemporal (95% CI: -75.06 to -5.17 µm, P = 0.0294), and superotemporal (95% CI: -76.82 to -18.51 µm, P = 0.0055) sectors. Average pRNFL thickness was significantly reduced compared with normative data in both the ipsilateral (95% CI: -40.76 to -11.69 µm, P = 0.0003) and the contralateral eye (95% CI: -38.46 to -5.83 µm, P = 0.0063). When only nasal and temporal data were analyzed, mean pRNFL thickness was still diminished compared with normative data (95% CI: -33.01 to -9.77 µm, P = 0.0012). CONCLUSIONS: Children presenting with optic atrophy, particularly with bitemporal optic atrophy, should have neuroimaging to exclude any underlying serious intracranial pathology.

Neuro-ophthalmic evaluation and management of pituitary disease.

Neuro-ophthalmic evaluation is a crucial component of the diagnostic and prognostic assessment of pituitary disease and compressive chiasmopathy, and can inform the timing of vision-restoring tumour resection surgery. The most common disease affecting the pituitary with neuro-ophthalmic implications are pituitary adenomas. Neuro-ophthalmic manifestations include decreased vision, abnormal colour vision and impaired visual field or diplopia. The recognition of these syndromes is critical to achieve early diagnosis and treatment and to improve prognosis. The pattern of vision loss in chiasmal compression is determined by the anatomical relationship between the pituitary lesion and optic chiasm, and potential visual field defects include bitemporal deficits, junctional scotomas, monocular cecocentral defects, and incongruous homonymous hemianopias. Rarer neuro-ophthalmic manifestations of pituitary disease include ophthalmoplegia, nystagmus, and obstructive hydrocephalus. There is growing evidence that demonstrates the strong diagnostic utility of optical coherence tomography (OCT) parameters in detecting the presence of compressive chiasmopathy, as well as the prognostic ability to predict the rate and degree of visual recovery following decompression surgery. Long-term neuro-ophthalmic monitoring is critical for detecting delayed vision loss following resection surgery, which may represent tumour recurrence or secondary complications.

Ocular manifestations of COVID-19.

There is an increasing body of knowledge regarding how COVID-19 may be associated with ocular disease of varying severity and duration. This article discusses the literature on the ocular manifestations associated with COVID-19, including appraisal of the current evidence, suggested mechanisms of action, associated comorbidities and risk factors, timing from initial infection to diagnosis and clinical red flags. The current literature primarily comprises case reports and case series which inevitably lack control groups and evidence to support causality. However, these early data have prompted the development of larger population-based and laboratory studies that are emerging. As new data become available, a better appraisal of the true effects of COVID-19 on the eye will be possible. While the COVID-19 pandemic was officially declared no longer a "global health emergency" by the World Health Organization (WHO) in May 2023, case numbers continue to rise. Reinfection with different variants is predicted to lead to a growing cumulative burden of disease, particularly as more chronic, multi-organ sequelae become apparent with potentially significant ocular implications. COVID-19 ocular manifestations are postulated to be due to three main mechanisms: firstly, there is a dysregulated immune response to the initial infection linked to inflammatory eye disease; secondly, patients with COVID-19 have a greater tendency towards a hypercoagulable state, leading to prothrombotic events; thirdly, patients with severe COVID-19 requiring hospitalisation and are immunosuppressed due to administered corticosteroids or comorbidities such as diabetes mellitus are at an increased risk of secondary infections, including endophthalmitis and rhino-orbital-mucormycosis. Reported ophthalmic associations with COVID-19, therefore, include a range of conditions such as conjunctivitis, scleritis, uveitis, endogenous endophthalmitis, corneal graft rejection, retinal artery and vein occlusion, non-arteritic ischaemic optic neuropathy, glaucoma, neurological and orbital sequelae. With the need to consider telemedicine consultation in view of COVID-19's infectivity, understanding the range of ocular conditions that may present during or following infection is essential to ensure patients are appropriately triaged, with prompt in-person ocular examination for management of potentially sight-threatening and life-threatening diseases.

Herpes Zoster Ophthalmicus Recurrence: Risk Factors and Long-Term Clinical Outcomes.

PURPOSE: To examine the frequency of recurrences, risk factors, and long-term clinical outcomes in subjects with herpes zoster ophthalmicus (HZO). DESIGN: Retrospective cohort study. METHODS: All subjects with acute HZO seen at a single center from 2006 to 2016 were included in the study. The primary outcome measure was eye disease recurrence. The secondary outcome measure was moderate vision loss (≤20/50). RESULTS: A total of 869 patients with acute HZO were identified, with a median follow-up time of 6.3 years (interquartile range 3.7-8.9 years). In all, 551 recurrences were observed, and at least 1 recurrence was seen in 200 subjects (23.0%), with uveitis (34.8%) being the most common. The median time to first recurrence was 3.5 months. Predictors of disease recurrence included immunosuppression (P = .026), higher presenting intraocular pressure (P = .001), corneal involvement (P = .001), and uveitis (P < .001) on multivariate analysis. Topical steroids were initiated in the first month of presentation in 437 subjects, and recurrence was observed in 184 (42.1%) of these subjects. Following cessation of topical steroid treatment, recurrence occurred after a median of 1.4 months (90% within 7 months). Moderate vision loss (≤20/50) occurred in 15.5%, 28.6%, 31.4%, 50.0%, and 57.4% of eyes with 0, 1, 2, 3, and 4 or more recurrences. CONCLUSIONS: Recurrence of HZO eye disease is common, with an increased risk of vision loss with more recurrences. These findings indicate the need for close monitoring for potential recurrences, especially after cessation of topical steroid treatment, and in individuals with identified risk factors for recurrence.

Neuro-ophthalmic complications of modern anti-cancer drugs.

PURPOSE: Targeted cancer therapies have been responsible for a dramatic shift in treatment strategies for cancer, and the number of drugs, classes, and indications are continually growing. Neuro-ophthalmic complications of these medications are an uncommon but important subset of adverse events which profoundly impact vision. This review aims to collate studies and reports of known neuro-ophthalmic complications of targeted therapies and describe their management. METHODS: The anti-cancer drugs included in the review were any drugs targeting specific molecules involved in the cancer disease process. PubMed, EMBASE, and Web of Science were searched using the generic names of each drug and keywords of neuro-ophthalmic conditions. The prescribing information published by the US Food and Drug Administration (FDA) for each drug was also reviewed. RESULTS: Several classes of targeted anti-cancer drugs were found to cause neuro-ophthalmic adverse effects. Immune checkpoint inhibitors are responsible for a raft of immune-related adverse events such as optic neuritis, ischemic optic neuropathy, PRES, and myasthenia gravis. Therapies with anti-VEGF activity can provoke posterior reversible leukoencephalopathy, which commonly presents with visual loss and can be fatal if not treated promptly. Inhibitors of BCR-ABL1, VEGF, ALK, and proteasomes have all been linked to optic nerve disorders which can have debilitating consequences for vision. CONCLUSION: The neuro-ophthalmic complications of modern anti-cancer drugs can limit or necessitate the withdrawal of these life-prolonging medications. Ophthalmologists should be alert for neuro-ophthalmic complications in these medications to facilitate prompt diagnosis and treatment and reduce the risk of severe and permanent consequences.

A review of neuro-ophthalmic sequelae following COVID-19 infection and vaccination.

Background: It has become increasingly clear that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect most organs in the human body, including the neurologic and ophthalmic systems. Vaccination campaigns have been developed at rapid pace around the world to protect the population from the fast-mutating virus. This review seeks to summarise current knowledge of the neuro-ophthalmic manifestations of both COVID-19 infection and vaccination. Evidence acquisition: Electronic searches for published literature were conducted using EMBASE and MEDLINE on the 30th of July 2023. The search strategy comprised of controlled vocabulary and free-text synonyms for the following terms in various combinations: "coronavirus, COVID-19, SARS-CoV-2, 2019-nCoV, vaccination, vaccine, immunisation and neuro-ophthalmology". No time range limits were set for the literature search. Published English abstracts for articles written in a different language were screened if available. Results: A total of 54 case reports and case series were selected for use in the final report. 34 articles documenting neuro-ophthalmic manifestations following COVID-19 infection and 20 articles with neuro-ophthalmic complications following COVID-19 vaccination were included, comprising of 79 patients in total. The most commonly occurring condition was optic neuritis, with 25 cases following COVID-19 infection and 27 cases following vaccination against COVID-19. Conclusions: The various COVID-19 vaccines that are currently available are part of the global effort to protect the most vulnerable of the human population. The incidence of neuro-ophthalmic consequences following infection with COVID-19 is hundred-folds higher and associated with more harrowing systemic effects than vaccination against the virus.

Optic atrophy in prematurity: pathophysiology and clinical features.

Optic atrophy is an important cause of visual impairment in children, and the aetiological profile has changed over time. Technological advancements led by neuroimaging of the visual pathway and imaging of the optic nerve with optical coherence tomography have accelerated the understanding of this condition. In the new millennium, an increasing prevalence of prematurity as a cause of optic atrophy in children has been highlighted. This new shift has been linked with increasing rates of premature births and improved neonatal survival of preterm infants. The available literature is limited to hospital and registry-based cohorts with modest sample sizes, methodological heterogeneity and selection bias limitations. Larger studies that are better designed are required to better understand the contribution of prematurity to the disease burden. In addition to considering other life-threatening aetiologies, screening for premature birth should be covered as part of a comprehensive history when evaluating a child with paediatric optic atrophy.

Patient factors associated with appointment non-attendance at an ophthalmology department in Aotearoa New Zealand.

AIM: Appointment non-attendance is a problem for medical outpatient clinics, which can result in interruption of continuity of care and poor health outcomes for patients. Furthermore, non-attendance creates a significant economic burden to the health sector. This study aimed to identify factors that are associated with appointment non-attendance in a large public ophthalmology clinic in Aotearoa New Zealand. METHODS: This study was a retrospective analysis of clinic non-attendance within Auckland District Health Board's (DHB) Ophthalmology Department between 1 January 2018 to 31 December 2019. Demographic data collected included: age, gender and ethnicity. Deprivation Index was calculated. Appointments were classified as new patients and follow-ups, and acute or routine. Categorical and continuous variables were analysed using logistic regression to assess likelihood of non-attendance. The research team's expertise and capacity align with the CONSIDER statement guidelines for Indigenous health and research. RESULTS: In total, 52,512 patients were scheduled to attend 227,028 outpatient visits, of which 20,580 visits (9.1%) were not attended. Median age of patients who received one or more scheduled appointments were 66.1 years (interquartile range [IQR] 46.9-77.9). Fifty-one point seven percent of patients were female. Ethnicity comprised 55.0% European, 7.9% Maori, 13.5% Pacific peoples, 20.6% Asian and 3.1% Other. Multivariate logistic regression analysis for all appointments showed that males (odds ratio [OR] 1.15 p<0.001), younger patients (OR 0.99 p<0.001), Maori (OR 2.69 p<0.001), Pacific peoples (OR 2.82 p<0.001), higher deprivation status (OR 1.06 p<0.001), new patient appointments (OR 1.61 p<0.001) and patients referred to acute clinics (OR 1.22 p<0.001) were more likely to not attend appointments. CONCLUSIONS: Maori and Pacific peoples disproportionately experience higher rates of appointment non-attendance. Further investigation of access barriers will enable Aotearoa New Zealand health strategy planning to develop targeted interventions addressing unmet patient needs of at-risk groups.

Nonarteritic Anterior Ischemic Optic Neuropathy After Cataract Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported to occur after cataract surgery. It is not clearly established whether cataract surgery increases the risk of NAION over baseline. EVIDENCE ACQUISITION: Medline, PubMed, Embase, and Cochrane Central registers were systematically searched for eligible studies reporting on postcataract surgery NAION (psNAION) within 1 year. All peer-reviewed publications with events n ≥ 10 were included. Pooled incidence and odds/hazard ratios and 95% confidence intervals (CIs) were extracted and calculated using random effect models for early and delayed psNAION. Time to event data were pooled for temporal analysis of psNAION events within the first year. This systematic review was registered (PROSPERO CRD42021274383). RESULTS: Nine articles met the selection criteria with five studies suitable for meta-analysis. A total of 320 psNAION cases, 1,307 spontaneous NAION (sNAION) cases, 1,587,691 cataract surgeries, and 1,538,897 noncataract surgery controls were included. Pooling of 63,823 cataract surgeries and 161,643 controls showed a hazard ratio of 4.6 (95% CI 2.7-7.8) of psNAION within 1 year of surgery. Pooled unadjusted incidence of psNAION within 2 months was 99.92 (95% CI 38.64-161.19) per 100,000/year, psNAION within 1 year was 32.36 (95% CI 9.38-55.34) per 100,000/year, and sNAION was 8.87 (95% CI 2.12-15.62) per 100,000/year. psNAION cases were older by a mean of 7.6 years; otherwise, pooled odds ratios for baseline risk factors in psNAION vs. sNAION cases were not statistically significant. psNAION within the first year peaked within 72 hrs and at 6 weeks after the surgery with 73% of cases occurring within 6 months. CONCLUSION: The risk of NAION after cataract surgery is four times greater within the first year and usually occurs within 6 months. However, the absolute risk remains low at 1 in 1,000-3,100 surgeries and is unlikely to warrant extra mention for consenting.

Current practice of trabeculectomy in a cohort of experienced glaucoma surgeons in Australia and New Zealand.

BACKGROUND/OBJECTIVES: To evaluate current routine trabeculectomy technique preferences among Australian and New Zealand Glaucoma Society surgeons regularly performing trabeculectomy surgery. SUBJECTS/METHODS: Survey of experienced surgeons who perform trabeculectomy. RESULTS: Forty-nine surgeons (33 male:16 female) participated in the survey. Trabeculectomy was performed as day surgery (39/47, 83.0%) under local anesthesia (44/47, 93.6%). The surgical techniques most commonly used were a corneal traction suture (44/47, 93.6%), fornix-based conjunctival flap (43/47, 91.5%) and half-thickness scleral flap (38/47, 81.0%). Mitomycin C antifibrotic agent was used in routine cases by 45/46 (97.8%) surgeons. Surgeons applied the antifibrotic agent under the Tenon layer with a pledget (36/46, 78.2%) with a concentration of 0.02% (37/46, 80.4%) for 2 (11/46, 23.9%) or 3 min (30/46, 65.2%). The Kelly (26/46, 56.5%) and the Khaw Descemet (19/46, 41.3%) punches were used to perform the sclerostomy. Most surgeons performed a peripheral iridectomy in all phakic patients (46/47, 97.9%), but less commonly in pseudophakic patients (34/47, 72.3%). Techniques for closure of the limbal conjunctival edge were quite varied with a combination of suturing including purse string (21/47, 57.4%), wing (20/47, 42.6%) and horizontal mattress sutures (33/47, 70.2%). Surgeons reviewed their routine patients four times in the first month (29/47, 61.7%) and continued the postoperative topical steroids for 3-4 months (28/47, 59.6%). CONCLUSIONS: Although a wide range of techniques for trabeculectomy exists among surgeons, there are consistent procedures currently in use to optimize patient outcomes. This report will assist surgeons in choosing which surgical techniques fit their best practice.

Eye Movements in Mild Traumatic Brain Injury: Clinical Challenges.

Mild traumatic brain injury (mTBI), also known as concussion, is a common injury which affects patients of all demographics. There is a global effort to accurately diagnose and identify patients at highest risk of prolonged symptom burden to facilitate appropriate rehabilitation efforts. Underreporting is common with large numbers not engaging with services, in addition to differences in treatment outcomes according to ethnicity, age, and gender. As patients recover, symptomology evolves which challenges rehabilitative efforts with no clear definition of 'recovered'. This review describes key areas in mTBI such as diagnostic challenges, epidemiology, prognosis, and pathophysiology which serves as an introduction to "Eye Movements in Mild Traumatic Brain Injury: Ocular Biomarkers."

Eye Movements in Mild Traumatic Brain Injury: Ocular Biomarkers.

Mild traumatic brain injury (mTBI, or concussion), results from direct and indirect trauma to the head (i.e. a closed injury of transmitted forces), with or without loss of consciousness. The current method of diagnosis is largely based on symptom assessment and clinical history. There is an urgent need to identify an objective biomarker which can not only detect injury, but inform prognosis and recovery. Ocular motor impairment is argued to be ubiquitous across mTBI subtypes and may serve as a valuable clinical biomarker with the recent advent of more affordable and portable eye tracking technology. Many groups have positively correlated the degree of ocular motor impairment to symptom severity with a minority attempting to validate these findings with diffusion tract imaging and functional MRI. However, numerous methodological issues limit the interpretation of results, preventing any singular ocular biomarker from prevailing. This review will comprehensively describe the anatomical susceptibility, clinical measurement, and current eye tracking literature surrounding saccades, smooth pursuit, vestibulo-ocular reflex, vergence, pupillary light reflex, and accommodation in mTBI.

Imaging of the optic nerve: technological advances and future prospects.

Over the past decade, ocular imaging strategies have greatly advanced the diagnosis and follow-up of patients with optic neuropathies. Developments in optic nerve imaging have specifically improved the care of patients with papilloedema and idiopathic intracranial hypertension, inflammatory optic neuropathies, and compressive optic neuropathies. For example, optic nerve imaging with optical coherence tomography (OCT) is now widely used as an outcome measure in clinical trials of neurological disorders (eg, demyelinating diseases), and OCT findings could be informative of disease progression in patients with various neurodegenerative disorders (eg, Alzheimer's disease or Parkinson's disease). In the past 5 years, multimodality optic nerve imaging has expanded to systematically include focused and wide-field colour and autofluorescence fundus photographs; various types of optic nerve, macular, and vascular OCT; and specific MRI techniques. Such multimodality imaging makes the diagnosis of optic neuropathies easier and provides objective information on optic nerve damage, which is useful for prognosis. Non-mydriatic ocular fundus cameras and OCT have become readily available in non-ophthalmic settings and could easily be implemented in neurological clinics and emergency departments, allowing for direct access to optic nerve imaging and enabling teleconsultations. In the future, these imaging studies could be used in association with artificial intelligence deep-learning systems, which are already transforming the field of ocular imaging.

Eye Movement Abnormalities in Glaucoma Patients: A Review.

Glaucoma is a common condition that relies on careful clinical assessment to diagnose and determine disease progression. There is growing evidence that glaucoma is associated not only with loss of retinal ganglion cells but also with degeneration of cortical and subcortical brain structures associated with vision and eye movements. The effect of glaucoma pathophysiology on eye movements is not well understood. In this review, we examine the evidence surrounding altered eye movements in glaucoma patients compared to healthy controls, with a focus on quantitative eye tracking studies measuring saccades, fixation, and optokinetic nystagmus in a range of visual tasks. The evidence suggests that glaucoma patients have alterations in several eye movement domains. Patients exhibit longer saccade latencies, which worsen with increasing glaucoma severity. Other saccadic abnormalities include lower saccade amplitude and velocity, and difficulty inhibiting reflexive saccades. Fixation is pathologically altered in glaucoma with reduced stability. Optokinetic nystagmus measures have also been shown to be abnormal. Complex visual tasks (eg reading, driving, and navigating obstacles), integrate these eye movements and result in behavioral adaptations. The review concludes with a summary of the evidence and recommendations for future research in this emerging field.

Prompt Antiviral Therapy Is Associated With Lower Risk of Cerebrovascular Accident Following Herpes Zoster Ophthalmicus.

PURPOSE: To examine risk factors associated with cerebrovascular accident (CVA) following herpes zoster ophthalmicus (HZO). DESIGN: Retrospective cohort study. METHODS: Review of medical records of all patients with HZO seen at the department of Ophthalmology, Auckland District Health Board, New Zealand, between January 1, 2006, and December 31, 2016. The main outcome measure was cerebrovascular accident within 12 months of diagnosis. RESULTS: A total of 869 patients diagnosed with HZO were included in the study. The median age at onset of HZO was 65.5 years (interquartile range [IQR] 52.9-75.4), and 52.5% (n=456) were male. Antiviral therapy was started in 765 participants (88.0%), not used in 95 (10.9%), and not documented in 9 participants (1.0%). Four hundred sixty-eight participants (54.9%) received prompt oral antiviral therapy (≤72 hours of rash onset). A CVA occurred in the 12 months following HZO in 14 patients (1.6%) and was most common in older patients, occurring in 2.5% aged ≥65 years, 0.7% aged 40-65 years, and 0.9% aged <40 years. Hazard of CVA was highest immediately following HZO, with median time to CVA of 2.3 months (IQR 0.8-5.9 months). Patients who received prompt acyclovir had a 76.2% lower hazard of CVA (0.9% vs 2.6%, P = .022) on multivariate analysis. CONCLUSIONS: Cerebrovascular accident occurs in a low proportion of individuals within 1 year following HZO. Antiviral treatment for HZO may reduce the risk of subsequent CVA when given within 72 hours of rash onset.